The goal of this research is to improve emergency department (ED) pain management for adults with sickle cell disease (SCD). Patients present to the ED for treatment of severe, painful vaso-occlusive crisis (VOC). There is no standard, evidence based approach to treating painful VOC. In August 2012 the National Heart, Lung, and Blood Institute released for public comment their Management of Sickle Cell Disease evidence- based recommendations that were developed with consensus panel expertise. Because of a lack of empirical data, most of the recommendations specific to VOC were based on consensus panel expertise. Recommendations included the use of a patient specific protocol (specific agents and doses for an individual patient) or a standard VOC analgesic protocol. Using the NHLBI expert panel recommended protocols, we will conduct a pilot RCT at two EDs and enroll 77 patients with approximately 160 ED visits. The purpose of this pilot RCT application is to collect the data necessary to design and execute a definitive RCT comparing patient specific protocols to a SCD standard protocol. Study outcomes are to examine the difference in the reduction in pain score from arrival in the ED to discharge (home or hospital admission), hospital admission, and other clinical (i.e., time to pain relief, improvement in pain score, patient satisfaction) and safety (respiratory and hemodynamic) outcomes. Study aims are to: 1. Develop and implement patient specific VOC protocols for patients randomized to this treatment arm; 2. Conduct a pilot RCT to determine the necessary sample size needed for a large RCT to compare the difference in reduction in pain score from arrival to discharge, hospitalization , clinical and safety outcomes, between subjects assigned randomly to a (1) standard SCD specific analgesic protocol, (control) and (2) patient-specific analgesic protocols. 3. Measure feasibility of methods and acceptability of and fidelity to protocols by evaluating optimal recruitment and retention strategies, and assessing ED providers (RN and MD) perceptions of facilitators and barriers to protocol use and protocol adherence. Upon completion, we will either be prepared to conduct a RCT implementing a specific VOC protocol or we will be able to provide additional evidence to support dissemination of the draft sickle cell guidelines.